The benzodiazepines are well-known central nervous system agents which are therapeutically used in the treatment of anxiety states, neuroses, tension states associated with organic conditions, irritability, as well as the treatment of alcoholics, expecially for the alleviation of the symptons of alcoholic withdrawal or the excited and combative episodes that occur during alcoholic intoxication, and to relieve the anixety and tension associated with alcoholic post-withdrawal.
At the present time, the benzodiazepines are administered by both the oral and the parenteral route. The oral route of administration is the most common in therapeutic practice, but sometimes it is not possible to achieve sufficiently high plasma concentrations to be effective, and some patients occasionally have an absorption malfunction. Moreover, oral administration is precluded for patients with gastrointestinal intolerance, or those in preparation for anesthesia or who have had gastrointestinal surgery.
The parenteral routes of administration, on the other hand, generally lead to very rapid rises in plasma concentration of the therapeutic agent. This is especially true of the intravenous route of administration, in which no delay in the rapid rise of plasma concentration is imposed by absorption. The intramuscular and subcutaneous routes have a fairly rapid during drug absorption profile, and so are likewise desirable routes of administration. However, parenteral administration is often accompanied by pain and irritation at the injection site. Moreover, parenteral routes of administration require sterilization of both the preparatives and the hypodermic syringes. A more significant problem with parenteral routes of administration is that except in a few unique instances, self-administration, which is possible in the case of the oral route, is not practical or even desirable with the parenteral routes.
All the above-mentioned factors hold true with regard to the oral and parenteral routes of administration of the benzodiazepines. Some of the benzodiazepines, as for example oxazepam and lorazepam, at present are not even available in parenteral dosage forms. Therefore, it would be highly desirable to have a dosage form for administration of benzodiazepines which has the ease of administration of the oral route with the rapid attainment of effective plasma concentrations possible with the parenteral routes, and without the disadvantages of either of these two common routes of administration.
It has now been unexpectedly found that the intraoral, i.e. buccal or sublingual, administration of benzodiazepines results in therapeutic effects indistinguishable from those of the parenteral dosage form.